Citations

Background and Objectives: The Family Medicine for America’s Health Workforce and Education Team aims to increase the number of medical students choosing family medicine to address the projected primary care physician shortage. This aim can be achieved by developing a well-trained primary care workforce. Our student- and resident-led FMAHealth work group aimed to identify factors that influenced fourth-year medical students’ choice to become family physicians. The secondary objective compared such factors between the 10 medical schools with the highest percentage of students matching into family medicine and non-top 10 medical schools. Methods: Fourth-year medical students nationwide participated in 90-minute virtual focus groups. Reviewers coded deidentified transcriptions and identified key themes and subthemes that were found to influence student choice. Results: Fifty-five medical students participated in focus groups over a 2-year period. Three key themes were found to influence students: perspective, choice, and exposure. Subthemes included: (1) the importance of high-quality preceptors practicing full-scope family medicine, (2) the value of a rural experience, and (3) institutional support to pursue family medicine. Physician compensation and loan repayment concerns were not major factors influencing student choice. Conclusions: Many factors influence student choice of family medicine including preceptors, clinical exposures, and institutional support. These factors varied by institution and many were found to be different between top 10 and non-top 10 schools. Addressing these factors will help increase students’ choice of family medicine and reduce the primary care shortage.

Selective internal radiation therapy with 90Y-TheraSphere or 90Y-SIRSphere is used in the treatment of unresectable hepatic malignancies. To the best of our knowledge, this is the first 90Y-TheraSpheres series. BTG International Canada Inc. provided nonradiated microspheres from the Nordion manufacturer. The histologic processed microspheres were colorless, refractile, polarizable, 20 to 30 μm in diameter, and an occasional internal bulls’-eye seen with the condenser out and an internal cross seen with polarized light. Identical microspheres were identified in 15 hepatectomy specimens from four centers between February 2016 and March 2018. The patients were usually male (male=10, female=5) with a mean age of 59 years. All patients had a prior diagnosis of hepatocellular carcinoma (HCC) and documented 90Y-TheraSphere (mean duration from last deployment=32 wk). All surgical pathology specimens in these 15 patients were reviewed, but the microspheres were only identified in the hepatectomy specimens. During manuscript preparation, one case of 90Y-TheraSpheres gastritis was prospectively identified from a separate patient with a history of HCC and 90Y-TheraSpheres. In conclusion, recognition of 90Y-TheraSpheres is important so that one may consider the possibility of a nearby malignancy and or establish the cause of the background inflammatory or radiation-related injury. These structures can be easy to miss because the subtle morphology is distinct from previously reported 90Y-SIRSphere. Clues to the diagnosis include a history of HCC and background radiation change. We report the characteristic morphology as microspheres that overlap in size with 90Y-SIRSphere, but can be differentiated based on 90Y-TheraSpheres’ colorless appearance with occasional internal bulls’-eyes with the condenser out and an internal cross with polarized light.

Abstract During development of pancreatic cancer, alternatively activated macrophages contribute to fibrogenesis, pancreatic intraepithelial neoplasia (PanIN) lesion growth, and generation of an immunosuppressive environment. Here, we show that the immunomodulatory agent pomalidomide depletes pancreatic lesion areas of alternatively activated macrophage populations. Pomalidomide treatment resulted in downregulation of interferon regulatory factor 4, a transcription factor for M2 macrophage polarization. Pomalidomide-induced absence of alternatively activated macrophages led to a decrease in fibrosis at PanIN lesions and in syngeneic tumors; this was due to generation of an inflammatory, immune-responsive environment with increased expression of IL1α and presence of activated (IFNγ-positive) CD4+ and CD8+ T-cell populations. Our results indicate that pomalidomide could be used to decrease fibrogenesis in pancreatic cancer and may be ideal as a combination treatment with chemotherapeutic drugs or other immunotherapies. Significance: These findings reveal new insights into how macrophage populations within the pancreatic cancer microenvironment can be modulated, providing the means to turn the microenvironment from immunosuppressive to immune-responsive.

AbstractA major challenge in the development of cancer nanomedicine is the inability for nanomaterials to efficiently penetrate and deliver therapeutic agents into solid tumors. Previous studies have shown that tumor vasculature and extracellular matrix regulate the transvascular and interstitial transport of nanoparticles, both critical for successfully delivering nanomedicine into solid tumors. Within the malignant tumor microenvironment, blood vessels are morphologically abnormal and functionally exhibit substantial permeability. Furthermore, the tumor extracellular matrix (ECM), unlike that of the normal tissue parenchyma, is densely packed with collagen. These pathophysiological properties greatly impede intratumoral delivery of nanomaterials. By using an antivascular endothelial growth factor receptor antibody, DC101, and an antitransforming growth factor β1 (TGF‐β1) antibody, normalization of the tumor vasculature and ECM is achieved, respectively, in a syngeneic murine glioma model. This normalization effect results in a more organized vascular network, improves tissue perfusion, and reduces collagen density, all of which contribute to enhanced nanoparticle delivery and distribution within tumors. These findings suggest that combined vascular and ECM normalization strategies can be used to remodel the tumor microenvironment and improve nanomedicine delivery into solid tumors, which has significant implications for developing more effective combinational therapeutic strategies using cancer nanomedicine.

Abstract Airway smooth muscle (ASM) regulation of airway structure and contractility is critical in fetal/neonatal physiology in health and disease. Fetal lungs experience higher Ca 2+ environment that may impact extracellular Ca 2+ ([Ca 2+ ] o ) sensing receptor (CaSR). Well‐known in the parathyroid gland, CaSR is also expressed in late embryonic lung mesenchyme. Using cells from 18‐22 week human fetal lungs, we tested the hypothesis that CaSR regulates intracellular Ca 2+ ([Ca 2+ ] i ) in fetal ASM (fASM). Compared with adult ASM, CaSR expression was higher in fASM, while fluorescence Ca 2+ imaging showed that [Ca 2+ ] i was more sensitive to altered [Ca 2+ ] o . The fASM [Ca 2+ ] i responses to histamine were also more sensitive to [Ca 2+ ] o (0–2 mM) compared with an adult, enhanced by calcimimetic R568 but blunted by calcilytic NPS2143. [Ca 2+ ] i was enhanced by endogenous CaSR agonist spermine (again higher sensitivity compared with adult). Inhibition of phospholipase C (U73122; siRNA) or inositol 1,4,5‐triphosphate receptor (Xestospongin C) blunted [Ca 2+ ] o sensitivity and R568 effects. NPS2143 potentiated U73122 effects. Store‐operated Ca 2+ entry was potentiated by R568. Traction force microscopy showed responsiveness of fASM cellular contractility to [Ca 2+ ] o and NPS2143. Separately, fASM proliferation showed sensitivity to [Ca 2+ ] o and NPS2143. These results demonstrate functional CaSR in developing ASM that modulates airway contractility and proliferation.

The American Association of Physicists in Medicine (AAPM) has established a comprehensive Code of Ethics for its members. The Code is a formal part of AAPM governance, maintained as Professional Policy 24, and includes both principles of ethical practice and the rules by which a complaint will be adjudicated. The structure and content of the Code have been crafted to also serve the much broader purpose of giving practical ethical guidance to AAPM members for making sound decisions in their professional lives. The Code is structured in four major parts: a Preamble, a set of ten guiding Principles, Guidelines that elucidate the application of the Principles in various practice settings, and the formal Complaint process. Guidelines have been included to address evolving social and cultural norms, such as the use of social media and the broadening scope of considerations important in an evolving workplace. The document presented here is the first major revision of the AAPM Code of Ethics since 2008. This revision was approved by the Board of Directors to become effective 1 January 2019.